Industry expectations from a regulatory perspective are evolving as the new Clinical Trial Information System (CTIS) for clinical trials in the European Union (EU) goes live. On 31 January 2022, the launching of the CTIS facilitated the meeting of the requirements of the Clinical Trials Regulation (CTR). Beginning 31 January 2023, study sponsors can apply only under the CTR instead of the prior regulation (the Clinical Trials Directive).
The CTR (EU) No 536/2014 is the new regulation that replaces and expands the EU Clinical Trials Directive 2001/20/EC. The new regulation focuses on three main aims - fostering a favorable environment for conducting clinical trials in the EU, ensuring the highest standards of safety for the study participants, and increasing transparency of clinical trial information i.e. data sharing. The next step for CTR is the Accelerating Clinical Trials in the EU (ACT EU) initiative that focuses on increasing transparency in data sharing among various study sponsors.
The CTIS is a digital portal and database built especially to facilitate the implementation of the CTR. Study sponsors can submit the applications using the portal and also send documents to regulatory authorities throughout the life cycle of their clinical trial. The member states of the EU will use this portal for conducting their daily business processes. The CTIS digital portal will streamline communication between study sponsors and member states of the EU.
Most study sponsors are dealing with a time-sensitive question - are we ready for the CTIS?
As of July 2022, 195 clinical trial applications were submitted through the CTIS. However in earlier years, each year approximately 4000 clinical trials are approved. Clearly, study sponsors are still seeking more information and reorganizing their internal processes to make submissions via the CTIS.
The CTR has introduced new standards of transparency and disclosure of in-process and completed trials. Study sponsors now have four major disclosure considerations before their clinical trial application (CTA) submissions. First, personal data and commercially confidential information (CCI) are exempt from disclosure. Study sponsors need to determine what constitutes the CCI for their studies. Secondly, public and non-public versions of documents need to be submitted simultaneously.
Next, after the approval of the study, the documents will become available to the general public. If a deferral was requested then the documents will not be published along with the public version of the document. Instead, the documents will be published per the approved deferral timelines. An additional note to remember is that the timelines for pediatric studies and adult studies are different. Lastly, now clinical trial documents need to include a plain language summary for Phase 2-4 trials within 12 months of the close of the trial.
Although there are four major disclosure considerations, each of them has several decision points (e.g. what constitutes the CCI?) and these decisions can have an impact on the entire lifecycle of the study. Study sponsors may benefit from having regulatory affairs teams in-house or consulting external agencies that can provide expert opinions about regulatory affairs. Since this is a time-sensitive endeavor, several study sponsors are currently looking for more information.
Some study sponsors struggle with finding reliable and clear information about the CTIS. The European Medicines Agency website is a good place to start. It includes various guideline documents and videos to inform about the new regulations. However, some of these rules can be complicated, and seeking advice from experienced professionals with several years of regulatory experience usually helps.
Recently at the Clinical Data Disclosure Day 2022, a virtual webinar series, Real Life Sciences (RLS) team presented the CTIS readiness webinar. It offered practical tools and reference materials to meet the disclosure-related requirements during the time crunch. Additionally RLS experts also shared insights about how to plan for the publication of trial documents under the CTR. For a copy of the recording Contact RLS.